Globally,ischemic stroke causes millions of deaths per year.The outcomes of ischemic stroke are largely determined by the amount of ischemia-related and reperfusion-related neuronal death in the infarct region.In the ...Globally,ischemic stroke causes millions of deaths per year.The outcomes of ischemic stroke are largely determined by the amount of ischemia-related and reperfusion-related neuronal death in the infarct region.In the infarct region,cell injuries follow either the regulated pathway involving precise signaling cascades,such as apoptosis and autophagy,or the nonregulated pathway,which is uncontrolled by any molecularly defined effector mechanisms such as necrosis.However,numerous studies have recently found that a certain type of necrosis can be regulated and potentially modified by drugs and is nonapoptotic;this type of necrosis is referred to as regulated necrosis.Depending on the signaling pathway,various elements of regulated necrosis contribute to the development of ischemic stroke,such as necroptosis,pyroptosis,ferroptosis,pathanatos,mitochondrial permeability transition pore-mediated necrosis and oncosis.In this review,we aim to summarize the underlying molecular mechanisms of regulated necrosis in ischemic stroke and explore the crosstalk and interplay among the diverse types of regulated necrosis.We believe that targeting these regulated necrosis pathways both pharmacologically and genetically in ischemiainduced neuronal death and protection could be an efficient strategy to increase neuronal survival and regeneration in ischemic stroke.展开更多
基金supported by the National Key Research and Development Program of China(No.2020YFC2008304)Natural Science Foundation of Henan Province(No.222300420350)+3 种基金National Natural Science Foundation of China(No.82204389),Medical Science and Technique Foundation of Henan Province(No.LHGJ20200310,SBGJ202102145)Foundation of Henan Educational Committee(No.21A310027,No.21A350014)National Natural Science Young Scientists Foundation of China(No.82200796)China Postdoctoral Science Foundation(No.2022M722901).
文摘Globally,ischemic stroke causes millions of deaths per year.The outcomes of ischemic stroke are largely determined by the amount of ischemia-related and reperfusion-related neuronal death in the infarct region.In the infarct region,cell injuries follow either the regulated pathway involving precise signaling cascades,such as apoptosis and autophagy,or the nonregulated pathway,which is uncontrolled by any molecularly defined effector mechanisms such as necrosis.However,numerous studies have recently found that a certain type of necrosis can be regulated and potentially modified by drugs and is nonapoptotic;this type of necrosis is referred to as regulated necrosis.Depending on the signaling pathway,various elements of regulated necrosis contribute to the development of ischemic stroke,such as necroptosis,pyroptosis,ferroptosis,pathanatos,mitochondrial permeability transition pore-mediated necrosis and oncosis.In this review,we aim to summarize the underlying molecular mechanisms of regulated necrosis in ischemic stroke and explore the crosstalk and interplay among the diverse types of regulated necrosis.We believe that targeting these regulated necrosis pathways both pharmacologically and genetically in ischemiainduced neuronal death and protection could be an efficient strategy to increase neuronal survival and regeneration in ischemic stroke.
